title: SOCS-1 mediates ubiquitylation and degradation of GM-CSF receptor.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and the related cytokines interleukin (IL)-3 and IL-5 regulate the production and functional activation of hematopoietic cells. GM-CSF acts on monocytes/macrophages and granulocytes, and several chronic inflammatory diseases and a number of haematological malignancies such as Juvenile myelomonocytic leukaemia (JMML) are associated with deregulated GM-CSF receptor (GMR) signaling. The downregulation of GMR downstream signaling is mediated in part by the clearance of activated GMR via the proteasome, which is dependent on the ubiquitylation of βc signaling subunit of GMR via an unknown E3 ubiquitin ligase. Here, we show that suppressor of cytokine signaling 1 (SOCS-1), best known for its ability to promote ubiquitin-mediated degradation of the non-receptor tyrosine kinase Janus kinase 2 (JAK2), also targets GMRβc for ubiquitin-mediated degradation and attenuates GM-CSF-induced downstream signaling.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Severa
authors.initials: S
authors.lastname: Bunda
authors.forename: Kamya
authors.initials: K
authors.lastname: Kommaraju
authors.forename: Pardeep
authors.initials: P
authors.lastname: Heir
authors.forename: Michael
authors.initials: M
authors.lastname: Ohh
mesh_terms: D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D010957:Plasmids / Q000235:genetics; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins